PURPOSE: The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in patients with diabetes mellitus (DM). The night's decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM. METHODS: Platelet aggregation was measured in blood samples from healthy individuals (n = 15) and type 2 DM patients (n = 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations. RESULTS: In healthy individuals, melatonin inhibited platelet aggregation in both higher (10-5 M) and lower concentrations (10-9 M) induced by ADP, ASPI, and TRAP (p < 0.001, p = 0.002, p = 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (p = 0.005, p = 0.045 and p = 0.048, respectively). CONCLUSION: Platelet aggregation was inhibited by melatonin in healthy individuals. In-vitro antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.

• Klíčová slova
• Acute myocardial infarction, Circadian variation, Diabetes mellitus, Melatonin, Platelet aggregation,
• MeSH
• adenosindifosfát farmakologie   MeSH
• agregace trombocytů fyziologie   MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• infarkt myokardu * MeSH
• inhibitory agregace trombocytů farmakologie   terapeutické užití   MeSH
• lidé MeSH
• melatonin * farmakologie   terapeutické užití   MeSH
• trombocyty fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosindifosfát MeSH
• inhibitory agregace trombocytů MeSH
• melatonin * MeSH

Melatonin has been reported to cause myocardial electrophysiological changes and prevent ventricular tachycardia or fibrillation (VT/VF) in ischemia and reperfusion. We sought to identify electrophysiological targets responsible for the melatonin antiarrhythmic action and to explore whether melatonin receptor-dependent pathways or its antioxidative properties are essential for these effects. Ischemia was induced in anesthetized rats given a placebo, melatonin, and/or luzindole (MT1/MT2 melatonin receptor blocker), and epicardial mapping with reperfusion VT/VFs assessment was performed. The oxidative stress assessment and Western blotting analysis were performed in the explanted hearts. Transmembrane potentials and ionic currents were recorded in cardiomyocytes with melatonin and/or luzindole application. Melatonin reduced reperfusion VT/VF incidence associated with local activation time in logistic regression analysis. Melatonin prevented ischemia-related conduction slowing and did not change the total connexin43 (Cx43) level or oxidative stress markers, but it increased the content of a phosphorylated Cx43 variant (P-Cx43368). Luzindole abolished the melatonin antiarrhythmic effect, slowed conduction, decreased total Cx43, protein kinase Cε and P-Cx43368 levels, and the IK1 current, and caused resting membrane potential (RMP) depolarization. Neither melatonin nor luzindole modified INa current. Thus, the antiarrhythmic effect of melatonin was mediated by the receptor-dependent enhancement of impulse conduction, which was associated with Cx43 phosphorylation and maintaining the RMP level.

• Klíčová slova
• conduction velocity, connexin-43, melatonin, post-ischemic arrhythmias, potassium current, rat heart, sodium current,
• MeSH
• antiarytmika farmakologie   terapeutické užití   MeSH
• kardiomyocyty metabolismus   MeSH
• konexin 43 * metabolismus   MeSH
• krysa rodu Rattus MeSH
• melatonin * farmakologie   terapeutické užití   MeSH
• melatoninové receptory metabolismus   MeSH
• srdeční arytmie farmakoterapie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiarytmika MeSH
• konexin 43 * MeSH
• luzindole MeSH Prohlížeč
• melatonin * MeSH
• melatoninové receptory MeSH

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and "ischemic" conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) (p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT (p = 0.001), whereas VT/VF incidence was associated with baseline ATs (p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation (p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.

• Klíčová slova
• arrhythmia, depolarization, ischemia, melatonin, oxidative stress, reperfusion, repolarization,
• MeSH
• antiarytmika farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• elektrofyziologické jevy účinky léků   MeSH
• elektrokardiografie účinky léků   MeSH
• fibrilace komor farmakoterapie   MeSH
• krysa rodu Rattus MeSH
• melatonin farmakologie   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu farmakoterapie   MeSH
• reperfuzní poškození farmakoterapie   MeSH
• srdeční arytmie farmakoterapie   MeSH
• srdeční elektrofyziologie metody   MeSH
• srdeční komory účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiarytmika MeSH
• antioxidancia MeSH
• melatonin MeSH